To transform the clinical management of cancer in the near term, it is essential to develop drugs in more precisely defined and biologically relevant patient groups. The practice of precision medicine, where the choice of treatment is based on the biologic profile of an individual patient’s tumor, requires analytically valid assays for the integral biomarker(s) on which the selection of treatment will be made. However, for many treatments, the complexities of identifying a predictive biomarker, the complexities of developing analytically valid assays and the evidence needed to show clinical utility are grossly underestimated. To this end, numerous innovative, multidisciplinary trials and programs have been developed, and the concept of phenogenomics has been established, to best leverage genomics in clinical practice.